Inflammatory biomarkers in sera of patients with intervertebral disc degeneration / Biomarcadores inflamatórios no plasma de pacientes com degeneração do disco intervertebral

ABSTRACT Objective: To evaluate intervertebral disc levels of inflammatory factor (interleukin 6) and proteinase activity (cathepsin B) in patients with a degenerative disease and serum levels of interleukin 6, serum cathepsin B activity and hyaluronic acid biomarkers. Methods: We conducted immunohistochemistry studies of intervertebral discs to analyze interleukin 6 and cathepsin B levels of patients with degenerative disease and spine fracture (Control Group) and to measure hyaluronic acid, interleukin 6 and cathepsin B activity from sera of intervertebral disc degeneration patients, fracture patients, and healthy individuals. Results: Interleukin 6 and cathepsin B seem to be related with physiopathology of intervertebral disc degeneration, since the levels of both were higher in discs of patients with intervertebral disc degeneration. Interleukin 6 and cathepsin B do not represent good biomarkers of degenerative intervertebral disc disease, since the level of such compounds is increased in the plasma of patients with fractures. Conclusion: Hyaluronic acid can be a biomarker for intervertebral disc degeneration, because hyaluronic acid levels were higher only in sera of patients with intervertebral disc degeneration.

RESUMO Objetivo: Avaliar os níveis de fatores inflamatórios nos discos intervertebrais (interleucina 6) e proteinase (catepsina B) em pacientes com doença degenerativa de disco intervertebral, além de verificar os níveis séricos de interleucina 6, ácido hialurônico e atividade sérica da catepsina B. Métodos: Foi realizado exame imuno-histoquímica dos discos intervertebrais de pacientes com doença degenerativa e fratura da coluna (Grupo Controle) e análise do plasma de pacientes com doença degenerativa de disco intervertebral. Como controle, foram utilizados plasma de pacientes com fraturas, além de indivíduos saudáveis. Resultados: Interleucina 6 e catepsina B sugerem relação com a fisiopatologia da doença degenerativa de disco intervertebral, uma vez que os níveis de ambos foram maiores nos discos de pacientes com doença degenerativa de disco intervertebral. Interleucina 6 e catepsina B não representam bons biomarcadores da doença degenerativa do disco intervertebral, já que também encontram níveis aumentados em plasma de pacientes com fratura. Conclusão: O ácido hialurônico é um possível biomarcador de doença degenerativa de disco intervertebral, porque os níveis de ácido hialurônico foram maiores apenas em plasma de pacientes com doença degenerativa de disco intervertebral.

Prospective evaluation of Chondroitin sulfate, Heparan sulfate and Hyaluronic acid in prostate cancer

ABSTRACT Purpose: The present study evaluates chondroitin sulfate (CS) and heparan sulfate (HS) in the urine and hyaluronic acid (HA) in the plasma of patients with prostate cancer before and after treatment compared to a control group. Materials and Methods: Plasma samples were used for HA dosage and urine for quantification of CS and HS from forty-four cancer patients and fourteen controls. Clinical, laboratory and radiological information were correlated with glycosaminoglycan quantification by statistical analysis. Results: Serum HA was significantly increased in cancer patients (39.68 ± 30.00 ng/ mL) compared to control group (15.04 ± 7.11 ng/mL; p=0.004) and was further increased in high-risk prostate cancer patients when compared to lower risk patients (p = 0.0214). Also, surgically treated individuals had a significant decrease in seric levels of heparan sulfate after surgical treatment, 31.05 ± 21.01 μg/mL (before surgery) and 23.14 ± 11.1 μg/mL (after surgery; p=0.029). There was no difference in the urinary CS and HS between prostate cancer patients and control group. Urinary CS in cancer patients was 27.32 ± 25.99 μg/mg creatinine while in the men unaffected by cancer it was 31.37 ± 28.37 μg/mg creatinine (p=0.4768). Urinary HS was 39.58 ± 32.81 μg/ mg creatinine and 35.29 ± 28.11 μg/mg creatinine, respectively, in cancer patients and control group (p=0.6252). Conclusions: Serum HA may be a useful biomarker for the diagnosis and prognosis of prostate cancer. However, urinary CS and HS did not altered in the present evaluation. Further studies are necessary to confirm these preliminary findings.

Hyaluronic acid in dermatomyositis and polymyositis: relationship with disease and cutaneous lesions

Abstract: Background: There are scarce studies in the literature about hyaluronic acid in systemic autoimmune myopathies. Objectives: To analyze the serum level of hyaluronic acid in patients with dermatomyositis and polymyositis. Methods: Cross-sectional study, single-center, that evaluated hyaluronic acid in 18 dermatomyositis and 15 polymyositis (Bohan and Peter criteria), newly diagnosed, with clinical and laboratory activity, with no previous drug treatment. The patients were also age-, gender- and ethnicity-matched to 36 healthy individuals. The hyaluronic acid was analyzed by ELISA/EIA kit anti-hyaluronic acid. Results: There was a higher serum level of hyaluronic acid in patients with autoimmune myopathies, in relation to control group (P<0.05). Moreover, the serum level of this glycosaminoglycan was higher in dermatomyositis, when compared to polymyositis. Both groups were comparable with regard to demographic, clinical and laboratory data, except for the presence of skin lesions in the first group. Study limitations. The presence of hyaluronic acid in cutaneous lesions, particularly of patients with dermatomyositis, was not analyzed neither quantified. In addition, due to disease rarity and the establishment of strict inclusion and exclusion criteria, there was a small sample in the present study. Conclusions: As an example of others systemic autoimmune diseases, it is possible that the hyaluronic acid is involved in the pathogenesis of autoimmune myopathies, and particularly when associated with cutaneous lesions.

New index for the diagnosis of liver fibrosis in Schistosomiasis mansoni / Novo índice biológico para o diagnóstico da fibrose hepática na Esquistossomose mansoni

ABSTRACT BACKGROUND Periportal fibrosis is the major pathological consequence of the Schistosoma mansoni infection. OBJECTIVE To evaluate the accuracy of serum markers and to construct an index to assess fibrosis. METHODS Patients (n=116) with schistosomiasis were evaluated by ultrasound scan and measurements of serum levels of aminotransferases, γ-glutamyl transferase, alkaline phosphatase, hyaluronic acid, cytokines and platelets. Ultrasound images were used to evaluate the fibrosis using Niamey's classification and identified 19 patients without periportal fibrosis (patterns A and B), 48 with mild to moderate fibrosis (C and D) and 49 with advanced fibrosis (E and F). RESULTS Using multivariate analysis, a model was created, which involved alkaline phosphatase and platelets and could separate patients with different patterns of fibrosis. This index showed a better performance in separating patients without fibrosis from with advanced periportal fibrosis. The biological index showed an area under the ROC curve of 1.000. Using values below the lowest or above the highest cut-off point, the presence or absence of advanced fibrosis could be predicted in all patients. CONCLUSION The index constructed can be used to separate patients with different patterns of periportal fibrosis, specially to predict advanced fibrosis in schistosomiasis patients.

RESUMO CONTEXTO A fibrose periportal é a maior consequência patológica da infecção pelo Schistosoma mansoni. OBJETIVO Avaliar a acurácia de marcadores séricos e construir um índice para avaliar a fibrose. MÉTODOS Pacientes (n=116) com esquistossomose foram avaliados pela ultrassonografia e dosados os níveis de aminotransferases, γ-glutamil transferase, fosfatase alcalina, ácido hialurônico, citocinas e plaquetas. Imagens de ultrasom foram utilizadas para avaliar a fibrose através de classificação de Niamey e identificados 19 pacientes sem fibrose periportal (padrão A e B), 48 com fibrose média a moderada (C e D) e 49 com fibrose avançada (E e F). RESULTADOS Através de análise multivariada, um modelo foi criado, que envolveu a fosfatase alcalina e plaquetas e conseguiu separar pacientes com diferentes padrões de fibrose periportal. Este índice mostrou um melhor desempenho em separar pacientes sem fibrose dos pacientes com fibrose avançada. O índice biológico mostrou uma área sob a curva ROC de 1,000. Usando valores infereiores e acima do ponto de corte, a presença ou ausência de fibrose avançada pode ser prevista em todos os pacientes. CONCLUSÃO O índice construído pode ser usado para separar os pacientes com diferentes padrões de fibrose periportal, especialmente para prever fibrose avançada em pacientes com esquistossomose.

Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV) paediatric patients (8-14 years) were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-β1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), hyaluronic acid (HA), procollagen type III amino-terminal peptide (PIIINP) and osteopontin (OPN), were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05). The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.

Bioactive hyaluronan fragment (hexasaccharide) detects specific hexa-binding proteins in human breast and stomach cancer: Possible role in tumorogenesis.

Hyaluronan (HA) is a component of extracellular matrix that influences cell-proliferation, migration, development, regeneration, normal tissue remodeling, tissues undergoing malignancy and tumor cell interaction. The widespread occurrence of HA binding proteins, their involvement in tissue organization and the control of cellular behavior are well documented. The low molecular mass HA fragments can also induce a variety of biological events, including chemokine gene expression, transcription factor expression and angiogenesis. It is believed that these fragments are more potent in cellular activities than high molecular mass HA. In this study, we isolated the various fragments by gel permeation chromatography of hyaluronidase digested HA and characterized by fluoro assisted carbohydrate electrophoresis (FACE) and matrix assisted laser desorption ionization analysis (MALDI). Detection and distribution of cellular receptors in invasive tumor tissues for HA polymer and HA fragments were determined both by Western blot and histochemistry. The study demonstrated the overexpression of HA-hexa binding protein in human tumors of breast and stomach and its involvement in tumorogenesis.

Role of hyaluronic acid and laminin as serum markers for predicting significant fibrosis in patients with chronic hepatitis B

OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of serum HA and LN as serum markers for predicting significant fibrosis in CHB patients. METHODS: Serum HA and LN levels of 87 patients with chronic hepatitis B and 19 blood donors were assayed by RIA. Liver fibrosis stages were determined according to the Metavir scoring-system. The diagnostic performances of all indexes were evaluated by the receiver operating characteristic (ROC) curves. RESULTS: Serum HA and LN concentrations increased significantly with the stage of hepatic fibrosis, which showed positive correlation with the stages of liver fibrosis (HA: r = 0.875, p < 0.001; LN: r = 0.610, p < 0.001). There were significant differences of serum HA and LN levels between F2-4 group in comparison with those in F0-F1 group (p < 0.001) and controls (p < 0.001), respectively. From ROC curves, 185.3 ng/mL as the optimal cut-off value of serum HA for diagnosis of significant fibrosis, giving its sensitivity, specificity, PPV, NPV, LR+, LR- and AC of 84.2 percent, 83.3 percent, 90.6 percent, 73.5 percent, 5.04, 0.19 and 83.9, respectively. While 132.7 ng/mL was the optimal cut-off value of serum LN, the sensitivity, specificity, PPV, NPV, LR+, LR- and AC were 71.9 percent, 80.0 percent, 87.2 percent, 60.0 percent, 3.59 percent, 0.35 percent and 74.7, respectively. Combinations of HA and LN by serial tests showed a perfect specificity and PPV of 100 percent, at the same time sensitivity declined to 63.2 percent and LR+ increased to 18.9, while parallel tests revealed a good sensitivity of 94.7 percent, NPV to 86.4 percent, and LR- declined to 0.08. CONCLUSIONS: Serum HA and LN concentrations showed positive correlation with the stages of liver fibrosis. Detection of serum HA and LN in predicting significant fibrosis showed good diagnostic performance, which would be further optimized by combination of the two indices. HA and LN would be clinically useful serum markers for predicting significant fibrosis in patients with chronic hepatitis B, when liver biopsy is contraindicated.

Diagnostic and prognostic value of some biochemical markers in early knee osteoarthritis

Osteoarthritis [OA]; the most common joint disease, is not only characterized by cartilage destruction; but also by alteration of bone and synovial tissue metabolism, though their relative importance in the initiation and progression of OA is still debated. To identify patients with a high risk for destructive OA, more sensitive techniques than plain X-rays are needed. To study the diagnostic and prognostic value of some biochemical markers serum hyaluronic acid [HA] and serum cartilage oligomeric matrix protein [COMP], high sensitive C-reactive protein [hs-CRP] in the included patients had early OA knees and their relation to disease progression. Sixty patients had early knee OA and 20 control subjects were included. WOMAC index, laboratory investigations [COMP, HA, hs-CRP] and radiological evaluation [Kellgren and Lawrence grading scale and Thomas compartmental score] were performed for each patient at baseline and after one year. HA was significantly higher in patients than controls [p > 0.001] with the highest specificity and positive predictive value. It was significantly correlated with COMP at baseline and after one year [p = 0.01]. The levels of HA at baseline correlated with its levels after one year [p > 0.001]. It also correlated with K-L grading score [p = 0.02]. COMP was significantly higher in patients than controls [p > 0.001]. It was significantly correlated with Thomas score after one year [p = 0.007]. Baseline levels of COMP correlated significantly with its levels after one year [p = 0.005]. The differences of the serum levels of hs-CRP at the baseline evaluation and after one year between patients and controls were not statistically significant [p = 0.4, 0.5, respectively]. The measurements of HA and COMP may be of diagnostic and prognostic value in differentiating patients with early joint destruction and in determining disease progression. A single biochemical marker has definitive diagnostic value and the combination with other biochemical markers as well as with clinical and radiographic data would most likely help to improve the clinical assessment of patients. Serum hs-CRP is not a good predictor of individual patient progression and has a poor sensitivity and specificity

Serum hyaluronic acid level does not reliably differentiate minimal and significant liver disease in chronic hepatitis C

To evaluate the predictive value of hyaluronic acid [HA] for the assessment of liver fibrosis and inflammation in chronic hepatitis C [CHC]. This cross-sectional study was conducted at Ziauddin University, Karachi, Pakistan from June 2006 to July 2010. Ninety-eight CHC patients, 52 [53%] males, and 46 [47%] females, with an age range of 20-60 years [mean 36.0 +/- 10.5] were recruited. Liver fibrosis was staged on a 5-point scale, F0 to F4, and inflammation was graded on a 4-point scale, A0 to A3. Patients were divided into minimal [F<2 and A<2] and significant [F >/= 2 or A >/= 2] overall disease groups. The HA was measured in the serum by ELISA. Diagnostic value was assessed through receiver operating characteristic [ROC] curve. Significant liver disease was present in 46 [47%] patients. Mean serum HA was significantly different among severity groups [p=0.001]. Area under ROC curve for overall disease was 0.716. Negative predictive value [NPV] for significant overall disease remained 71% at a low HA level of 20 ng/mL. Positive predictive value [PPV] of 85% was obtained at 60 ng/mL and 100% at 120 ng/mL. Those high levels were present in 15% and 10% of the patients. Serum HA levels showed a low NPV for significant liver disease. An acceptable PPV was found only in a small proportion of the patients. Hyaluronic acid may not be regarded as a reliable marker for making treatment decisions

Hyaluronic acid in the evaluation of liver fibrosis in patients with hepatitis C on haemodialysis

BACKGROUND: This study evaluated the role of HA as a marker of liver fibrosis in patients with hepatitis C on haemodialysis. METHODS: This is a cross-sectional study in which 52 patients were divided into two groups: Group 1: patients with hepatitis C and end-stage renal disease (ESRD) undergoing haemodialysis (n = 23); and Group 2: patients with hepatitis C without ESRD (n = 29). Plasma levels of HA were associated with histological data of the samples obtained by liver biopsy and classified by METAVIR group scoring system. RESULTS: Higher plasma levels were significantly correlated to significant liver fibrosis (METAVIR > F2). In Group 1, the HA cutoff to discriminate significant fibrosis was 984.8 ng/mL, with accuracy, sensitivity and specificity of 80.8 percent, 83.0 percent, and 70.0 percent, respectively. In Group 2, the HA cutoff was 222.3 ng/mL, with accuracy, sensitivity and specificity of 74.5 percent, 70.0 percent, and 94.0 percent, respectively. CONCLUSION: HA was an accurate noninvasive marker in predicting significant fibrosis in patients with hepatitis C on haemodialysis.

Serum hyaluronan and collagen IV as non-invasive markers of liver fibrosis in patients from an endemic area for schistosomiasis mansoni: a field-based study in Brazil

Non-invasive markers of fibrosis have been used to diagnose liver fibrosis in a variety of diseases. Hyaluronic acid (HA) and collagen IV (C-IV) levels were measured in the sera of patients from an endemic area for schistosomiasis in Brazil to diagnose and to rank the intensity of liver fibrosis. Seventy-nine adult patients with schistosomiasis, in the age range of 21-82 years (49 ± 13.4) were submitted to clinical and ultrasonographic examinations. Ultrasound was employed to diagnose and categorise liver fibrosis according to World Health Organization patterns. Serum HA and C-IV levels were measured using commercial ELISA kits. Ultrasound revealed six patients with intense liver fibrosis, 21 with moderate, 23 with light and 29 without. Serum HA was able to separate individuals with fibrosis from those without (p < 0.001) and light from intense fibrosis (p = 0.029), but C-IV was not (p = 0.692). The HA diagnostic accuracy for fibrosis was 0.89. The 115.4 ng/mL cut-off level diagnosed patients with fibrosis (sensitivity 0.98, specificity 0.64). HA correlated positively with portal hypertension. Periportal fibrosis (subjective evaluation), age and collateral circulation predicted HA increase. In conclusion, we propose that serum HA can be used to identify patients with liver fibrosis in an endemic area for schistosomiasis mansoni in Brazil.

suggested algorithm for using serum biomarkers for the diagnosis of liver fibrosis in chronic hepatitis C infection

Hepatitis C virus infection [HCV] is endemic in Egypt. Liver biopsy is the gold standard for diagnosis and staging of fibrosis in chronic hepatitis C patients. However, it is invasive, associated with sampling error and poses potential complications. A non-invasive alternative is needed. This assessed the accuracy of certain biochemical markers and ultaronography in predicting the stage of fibrosis in chronic hepatitis C patients. Sixty five patients with chronic HCV were enrolled. Ultrasonographic examination, complete blood count and liver function tests were done. Serum levels of hyaluronic acid [HA] and YKL-40 [a 40-kDa glycoprotein produced by stellate cells] were determined. Liver biopsy was done. Fibrosis was correlated with biochemical markers and ultrasonographic findings. Histopathological examination showed that 39 patients [60%] had F1, nine [14%] had F2, 17 [26%] had F3 and none had F0 or F4 scores. A value of alanine aminotransferase [ALT] index <0.38, HA <9.7 ng - ml[-1] or portal vein [PV] cross-sectional area <25.8 mm[2] excluded significant fibroses [>/= F2]. A value of aspartate aminotransferase [AST] + ALT<39.5 or ratio of AST index to the platelet count [APRI] <0.235 or HA x 100 per platelet [Plt] < 9.534 excluded the presence of advanced fibrosis with 100% negative predictive value [NPV]. Using these values, advanced fibrosis could be excluded in 72% of our patients. An APRI value of >/= 1.1 can diagnose advanced fibrosis with 100% positive predictive value [PPV] in 10%of our patients. Hence, only 18% of our patients in whom liver biopsy was recommended were not classified by these parameters. YKL-40 did not help in the diagnosis of advanced fibrosis. Applying a simple algorithm based on ALT, AST, platelet count, PV cross-sectional area, in addition to HA level may eliminate the need for liver biopsies in more than 80% of chronic HCV patients

Serum levels of hyaluronic acid [HA] and cartilage oligomeric matrix protein [COMP] as predictors of disease progression in rheumatoid arthritis

To measure the serum concentrations of specific cartilage and bone molecules reflecting tissue turnover to investigate disease activity. The study included 30 rheumatoid arthritis [RA] patients with age range 42 - 66 years. Sixteen patients had rapid erosive disease and fourteen had slow erosive, compared with 20 matched apparently healthy volunteers. All studied individuals were subjected to full history taking, clinical examination and laboratory investigations including measurement of serum levels of cartilage oligomeric matrix protein [COMP], hyaluronic acid [HA], high sensitive C- reactive protein [CRP], erythrocyte sedimentation rate [ESR] and RF concentration as well as measurement of activity of RA by disease activity score [DAS] 28 joint counts. The study showed a significantly higher values of COMP, HA, CRP and ESR in slow erosive [p<0.001] and rapid erosive [p<0.0001] RA patients when compared to controls. There were significantly higher values of COMP, HA, CRP and ESR in rapid erosive RA patients compared to slow erosive RA patients. A significant positive correlation between serum levels of COMP and HA and age, disease duration, Larsen score, DAS and CRP and ESR was found. Also there was a significant positive correlation between serum levels of COMP and HA [r = 0.674, p<0.01]. It could be concluded that the measurement of some serological biomarkers that reflect bone and cartilage destruction in RA patients, could be used to investigate disease activity and increase the knowledge of the basic pathophysiology of joint disease

Usefulness of Non-invasive Markers for Predicting Significant Fibrosis in Patients with Chronic Liver Disease

The purpose of this prospective study was to verify and compare the strengths of various blood markers and fibrosis models in predicting significant liver fibrosis. One hundred fifty-eight patients with chronic liver disease who underwent liver biopsy were enrolled. The mean age was 41 yr and male patients accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%) and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were assessed according to the Batts and Ludwig scoring system. Significant fibrosis was defined as > or =F2. Sixteen blood markers were measured along with liver biopsy, and estimates of hepatic fibrosis were calculated using various predictive models. Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106 cases (67.1%). On multivariate analysis, alpha2-macroglobulin, hyaluronic acid, and haptoglobin were found to be independently related to significant hepatic fibrosis. A new predictive model was constructed based on these variables, and its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In conclusion, alpha2-macroglobulin, hyaluronic acid, and haptoglobin levels are independent predictors for significant hepatic fibrosis in chronic liver disease.

Effect of pentoxifylline on serum hyaluronic acid in patients with non-alcoholic fatty liver disease

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most types of chronic liver diseases. Non-alcoholic fatty liver disease [NAFLD] can be associated with progressive hepatic fibrosis. In this study we evaluated the effect of pentoxifylline [PTX] on serum hyaluronic acid [HA] levels as a marker of fibrosis. In this study we included 30 subjects [14 males and 16 females], divided into three groups. The NAFLD group included 20 patients with fatty livers as shown by ultrasound examination. Patients were randomised into a placebo group of 10 patients who received a placebo, and a pentoxifylline PTX group of 10 patients who received pentoxifylline at 400 mg/day for 6 months. The control group included 10 normal individuals. In the NAFLD group the mean value of the base line serum HA was 133 +/- 150.48, while in the control group it was 33.5 +/- 10.01; the difference between the groups was statistically significant [p < 0.001]. The mean value of the base line serum HA in the PTX treated group was 169.5 +/- 156.19, while after 6 months of treatment it was 59 +/- 44.34, with a statistically significant difference [p = 0.007]. In the placebo treated group the mean value of the base line serum HA was 96.5 +/- 143.004, while after 6 months of treatment it was 59.7 +/- 44.29; this difference was not statistically significant [p = 0.594]. Our showed that, when administered for 6 months, PTX caused a significant decline in HA levels, which may be an index reflecting improvement of hepatic fibrosis. Further investigations should be conducted with a large number of patients to confirm our and correlate this with histological findings

possible beneficial effect of angiotensin II receptor antagonist [Losartan] in experimental-hepatic fibrosis in albino rats. histological immunohistochemical and biochemical study

Hepatic fibrosis is a histological change caused by liver inliammation and characterized by accuix of extracellular matrix protein [ECM]. Losartan is one class of drugs that inhibit the action of angiotensin II [A' H at its receptors. It has been used as antihypertensive in human. Was to clarify the beneficial effect of losartan in experimental liver fibrosis by bile duct li-z. Forty adult male albino rats were divided into four equal groups; GI [control], Gil operated], Gill [bile duct ligated, BDL] and G VI received losartan at a dose of 5 mg/kg daily after BDL. After fc weeks, blood samples were collected for estimation of serum bilirubin [SB], alanine aminotransferase [ALT], aspare aminotransferase [AST], alkaline phosphatase [ALP] and serum hyaluronic acid [SHA]. Rats were sacrificed and th livers were processed for estimation of hydroxyproline and for histological study. Paraffin sections were stained b H and F, Masson's trichrome and other sections were stained immunohistochemically for desmin. Revealed elevated liver enzymes, serum and tissue fibrosis markers [hyaluronic acid and hydrox-cr together with dramatic histological changes in liver sections of G III [BDL]. Administration of Losartan after BDL C-V showed improvement of biochemical analysis of liver enzymes, fibrosis markers and amelioration of the his o1oria changes of hepatic tissues. Moderate expression of desmin from hepatic stellate cells [HSCs] was also evident Fr this study. That losartan has a benifical effect in liver fibrosis induced by BDL. However, further study for its usefulness in human hepatic fibrosis is recommended

Elevated serum hyaluronic acid and interleukin-6 levels in patients with mushroom poisoning admitted to the emergency department

To assess the possible use of hyaluronic acid [HA] and interleukin-6 [IL-6] together as a biochemical marker of liver damage in mushroom poisoning [MP]. We prospectively studied patients with MP who were admitted to the emergency service, between April 2005 and April 2007, Samsun, Turkey. Twenty-seven patients with MP were included in the study. Serum HA and IL-6 levels of the patients were determined using enzyme-linked immunosorbent assay daily for a total of 3 days. Ten healthy adults were included in the study to serve as controls. The patients were divided into survivors, and non-survivors. There was no significant difference between the patients and controls with respect to serum HA levels on admission [p > 0.05]. However, IL-6 levels on admission were significantly higher in the patients than the control group [p < 0.01]. Serum HA and IL-6 levels on admission, and the following days were significantly higher in non-surviving patients [n = 5] than in surviving patients [n = 22] [p < 0.05]. There was a significant correlation between HA and IL-6 [r = 0.42, p < 0.05] on admission. The HA concentration was also significantly correlated with aspartate aminotransferase, alanine aminotransferase, and creatinine levels during the observation period. Serum HA and IL-6 levels increased in non-surviving patients throughout the period of observation. Increased serum HA and IL-6 levels are associated with hepatic damage in acute MP. Hyaluronic acid may be a useful marker in the assessment of MP-induced acute liver failure in clinical practice

The value of serum retinol-binding protein 4 levels for determining disease severity in patients with chronic liver disease / 대한간학회지

BACKGROUNDS/AIMS: Serum retinol-binding protein 4 (RBP4) is known to be a specific transport protein for retinol, and has recently been reported to be associated with insulin resistance. Hyaluronic acid (HA) is a well-known marker of liver fibrosis. In this study, the degree to which serum RBP4 levels can be used to predict disease severity in patients with chronic liver disease (CLD) was evaluated. METHODS: Serum levels of RBP4 and HA were measured in 573 CLD patients [235 with chronic hepatitis (CH), 230 with liver cirrhosis Child-Pugh grade (Child) A, and 108 with liver cirrhosis with Child B and C] and 40 normal controls. RESULTS: The mean age of the whole cohort was 53.1 years and the causes of CLD were hepatitis B virus (61.9%), hepatitis C virus (9.8%), alcohol (9.0%), and nonalcoholic steatohepatitis (3.8%). Serum levels of RBP4 significantly reduced and HA increased with disease condition, from none (normal controls) to advanced cirrhosis (normal control: RBP4 4.3+/-0.1 mg/dL, HA 25.3+/-28.1 ng/mL; CH: RBP4 3.6+/-0.1 mg/dL, HA 75.5+/-7.8 ng/mL; cirrhosis with Child A: RBP4 2.6+/-0.1 mg/dL, HA 184.4+/-14.5 ng/mL; and cirrhosis with Child B and C: RBP4 1.6+/-0.1 mg/dL, HA 656.5+/-86.7 ng/mL; P<0.001, respectively). Serum RBP4 level was a distinguishing factor at the early stage of CLD between CH and Child A cirrhosis (post-hoc test; P<0.001) and was correlated with histological fibrosis score (n=80, P<0.05) and several biochemical factors. Antiviral therapy (n=45, median interval 1,205 days) resulted in an improvement in serum RBP4 levels (P=0.001). CONCLUSIONS: The results of our study suggest that RBP4 is a serologic marker for disease severity in patients with CLD. It could also be useful as an early marker of CLD and of the relative success of antiviral therapy.

Comparison of various noninvasive serum markers of liver fibrosis in chronic viral liver disease / 대한간학회지

BACKGROUND/AIMS: The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. METHODS: We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. RESULTS: There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (> or =F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (> or =F3). CONCLUSIONS: All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis.

The effect of doxycycline on canine hip osteoarthritis: design of a 6-months clinical trial

Twenty-five dogs were included in a randomized, double-blind trial to assess the efficacy of doxycycline (DOX) orally administered twice a day at 4 mg/kg/day (n = 12) for the treatment of osteoarthritis of the hip. Chondroitin sulfate (CS; 525 mg/day) was used as a positive control (n = 13). Dogs were re-examined monthly for 6 months after initiation of treatment. The assessment protocol included clinical score, radiographic findings and serum osteoarthritis biomarkers. Dogs treated with DOX showed statistically significant improvements (p < 0.05) in lameness, joint mobility, pain on palpation, weight-bearing and overall score at 2, 6, 4, 4 and 4 months, respectively, after treatment. Biomarker levels of CS-WF6 epitope and hyaluronan were significantly increased and decreased (p < 0.05) at 2 and 3 months after treatment compared to pretreatment. These results showed that DOX had a positive therapeutic effect in dogs with osteoarthritis.